Critical Reviews http://cro.sagepub.

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Analysis of Pulpal Reactions to Restorative Procedures, Materials, Pulp Capping, and Future Therapies
Peter E. Murray, L. Jack Windsor, Thomas W. Smyth, Abeer A. Hafez and Charles F. Cox CROBM 2002 13: 509 DOI: 10.1177/154411130201300607 The online version of this article can be found at: http://cro.sagepub.com/content/13/6/509

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2002).5 million US restorations requiring root canal therapy (NIDCR. healing defects. the avoidance of post-operative complications with conventional therapies requires attention to numerous aspects of treatment highlighted in this review. by remineralizing caries lesions. stimulate. Cox Department of Restorative Dentistry. and millions of dental and oral craniofacial procedures. 2000). 500. 1999). Consequently. a high proportion of these teeth develop symptoms requiring endodontic treatment (Zöllner and Gaengler. University of Southern California. In the United States. CT 06105 Abeer A. 2002). Patient demand for tissue engineering therapy is staggering in both scope and cost. Currently. MATERIALS. bacterial leakage. Baum et al. it is necessary to evaluate the biological changes taking place in teeth to help optimize current treatment regimens. ranging from tooth restorations to major reconstruction of facial soft and mineralized tissues (National Institute of Dental and Craniofacial Research [NIDCR]. and restoring injured or replacing lost teeth. inflammation. 2011 For personal use only. until these therapies can be introduced clinically. This rate of treatment failure suggests that current restorative regimes are not yet optimized and have a potential for improvement. 2001a). Hafez School of Dentistry. AND FUTURE THERAPIES Peter E. with 1. ABSTRACT: Every year. and genetically alter disease pathogens to help eradicate caries and periodontitis (Hillman et al.ANALYSIS OF PULPAL REACTIONS TO RESTORATIVE PROCEDURES. and/or stimulation of mineralized tissue formation. 2000a). Los Angeles. $400 billion is spent treating Americans suffering some type of tissue loss or end-stage organ failure. of 290 million restorations. dental materials. *corresponding author. clinical experience or empirical evidence is used to diagnose dental problems requiring treatment. Hartford. this review will examine pulp injury and healing reactions to different restorative variables. 2002). or regeneration of cells. bacterial microleakage. No other uses without permission. it is estimated that. Los Angeles. 1998. However. 1998).com by guest on March 18. Smyth Department of Dentistry. Indiana University School of Dentistry.. CA 90089-0641 Charles F. and oral tissues (Baum and Mooney. 2000). There is limited information regarding sources of pulp injury. University of California at Los Angeles. 13(6):509-520 (2002) Burke et al. and neoplastic or infectious diseases is expected to solve many dental problems. Indianapolis. cavity restoration. and their proper use to avoid post-operative complications were investigated from a biological perspective. Cavity preparation. 290 million fillings are T (I) Introduction he regeneration or replacement of oral tissues affected by inherited disorders. unparalleled advances in restorative dentistry are set to take place with the availability of artificial teeth. 1995). Often. although these factors often create healing problems. or augment natural regenerative processes to accomplish therapy by tissue engineering. vaccinating against caries and oral diseases. 1994. Francis Hospital and Medical Center. two-thirds of these involve the replacement of failed restorations. and pulp inflammation. Two-thirds of all restorative dentistry involves the replacement of failed restorations (Maupome and Sheiham. Key words. CA 90095-1668 placed each year in the United States. Avoidance of tooth-healing complications requires examination of surgical trauma and injuries caused by a failure to use materials and procedures congruent with the natural regenerative activity of teeth (Murray et al. Therefore. growth factors. This might solve major dental problems. Murray* L. this review will investigate those aspects of restorative dentistry Crit Rev Oral Biol Med Downloaded from cro. bone. petmurra@iupui. produce vaccinations against viruses (Baum and O'Connell. trauma. despite the effectiveness of preventive dentistry and dental health care. and to use.000 joint replacements. Jack Windsor Department of Oral Biology. International and American Associations for Dental Research 509 . Within the next 25 years.000 organ transplants. selection of restorative materials. and millions of teeth are extracted. IN 46202-5186. 200 million are replacements for failed restorations (Arnst and Carey. because scientific evidence is lacking (Mjör. Consequently. 2002). Smith et al. 1121 West Michigan Street.sagepub. Improvements in the success of restorative treatments may be possible if caries management strategies..edu Thomas W.. The application of tissue engineering approaches to restorative dentistry will require the transplantation.. 2002). as well as the ability of growth factors to stimulate dental repair (Murray and Smith. regenerate lost tissues (Becker. 2000. This includes 20. replacement. School of Dentistry. organs. St. PULP CAPPING. Each year.

If demineralization stops. risk of pulp injury and exposure. fluo- (C) AMELOBLAST STEM CELL THERAPY AND TRANSPLANTATION OF ENAMEL The outer enamel layer of teeth is more than 95% mineral. 1998). The goals of treatment are to reduce the etiologic microbiota and contributing risk factors to halt the caries decay process and stimulate remineralization. Other matrix proteins. and TGF 1 (Tziafas et al. rapidly progressing lesions can overwhelm pulp-defensive responses and cause severe pulp injuries (Bjørndal and Mjör. These developments in caries treatment planning demonstrate how the natural remineralizing activity of teeth can be used to optimize restorative treatment. it can be either slowly or rapidly progressing (Bjørndal and Darvann. especially those of the transforming growth factor-beta (TGF ) family. commonly mutans streptococci and lactobacilli. it is important to formulate tissue-engineering protocols without delay. (A) OPTIMIZATION OF CARIES LESION TREATMENT Caries is cited as the most common reason for the need to restore teeth (Deligeorgi et al. for the management of caries. function. and accidental trauma. because the development phase of these new therapies is measured in decades. 2001). because the selection of approach can mediate the quantity of caries excavation. where they remain protected in an active form through interaction with other components of the dentin matrix (Smith et al. 2001). Growth factors. This can prevent extensive pulp injury by leaving firm but stained carious dentin at the cavity floor during excavation. 1997). Caries activity can be subdivided according to the rate of tooth demineralization. 1998).. or for esthetic reasons (Kihn and Barnes. and the pulp injury can be minimal. It is recommended to use caries detector dyes to distinguish the unstained remineralizable dentin that should not be excavated (Fusayama and Terachima. a step-wise excavation approach may be used (Bjørndal and Thylstrup. 2000). This dentin is often remineralizable (ten Cate. as can application of cavity-etching agents and restorative materials (Smith et al. 1995).. bone morphogenic proteins (Rutherford.. 1983). 1996). 1998). these growth factors may play key roles in signaling many of the events of tertiary dentinogenesis.. but the use of these dyes may lead to excessive removal of tooth tissues (I. are important in cellular signaling for odontoblast differentiation and stimulation of dentin matrix secretion. 2001). Minimally invasive procedures to treat small caries lesions are proving popular. International and American Associations for Dental Research . the enamel consists of a protein matrix that forms the framework for mineral deposition (Diekwisch et al. 2000). and it is uncertain exactly how this technology might be applied to solve many common dental problems.sagepub. 1972). Dental caries is a process that brings about a progressive acid-demineralization of the inorganic component of the tooth. a response of pulp-dentin repair. and the stepwise excavation of carious tissues can provide pulp protection by stimulating the remineralization of hard carious dentin and reactionary dentin (Leksell et al. 1995a). The selection of either treatment strategy is relevant to the risk of creating pulp complications. a caries lesion is regarded as "arrested"... it is likely that much of the therapeutic effect of calcium hydroxide may be due to its extraction of growth factors from the dentin matrix (Smith et al. It will also discuss how the natural regeneration of teeth could serve as the basis for tissue engineering approaches to solve common restorative problems. Transplants of ameloblasts and artificial enamel to the outer surfaces of teeth could replace the porcelain veneers and dental materials currently applied to restore tooth structure following caries. 2000). Dentin contains many proteins capable of stimulating tissue responses. including tuftelin and ameloblastin. (B) GROWTH FACTOR THERAPY TO STIMULATE TISSUE REGENERATION BENEATH CARIES If tissue engineering is to have a significant impact on restorative dentistry. Tissue engineering is in the early stages of development.. Carious demineralization of the dental tissues can lead to their release.. Nevertheless. Once released. (II) Treatment of Caries A caries lesion is initiated when micro-organisms in dental plaque. Indeed. and selection of capping materials. but has multifactorial etiology (Glossary of Operative Dentistry Terms. because this approach may be advantageous to prevent lesion progression (White and Eakle. personal communication). However. accompanied by an enzymatic disintegration of the organic portion. ferment carbohydrates (mainly sugars) to produce acid (Featherstone. Isolating ameloblast progenitor cells and replicating the natural enamel-forming process in threedimensional culture by the use of growth factors to stimulate enamel secretion offer the potential for transplantation. 1998). disease..A. However.. 1996). These growth factors are secreted by odontoblasts and deposited within the dentin matrix (Roberts-Clark and Smith. No other uses without permission. 1995). and esthetic appearance and to prevent the recurrence of caries (Lutz et al. or incorporating them into restorative materials to stimulate dentin and pulp regeneration. it must primarily focus on providing effective treatments for remineralizing caries lesions and arresting or reversing tooth decay. size of cavity preparation. it is difficult to achieve the correct balance between an eagerness to remove the lesion and the continued monitoring of lesion progression.com by guest on March 18. ride-containing pulp-capping materials. The advantage of 13(6):509-520 (2002) 510 Crit Rev Oral Biol Med Downloaded from cro.. 2000). 2001). have been observed to remineralize adjacent caries (Donly and Grandgenett. Amelogenin secreted by ameloblasts accounts for 90% of the enamel matrix mineral (ZeichnerDavid et al. Furthermore. This indicates the potential for the addition of growth factors prior to pulp capping. The defense and healing of tooth pulp tissue are more effective in response to slowly progressing or arrested lesions.. Although pediatric dentists continue to apply pit-and-fissure sealants to erupting permanent teeth. During formative stages. if the caries lesion is "active". The addition of purified dentin protein fractions (Smith et al. have recently been identified and cloned (Takahashi et al. 1998) following cavity preparation—all have stimulated an increase in tertiary dentin matrix secretion. erosion. this is not done in many general practices. 1998). simple sealing of caries lesions with composite resin or resin/amalgam techniques has been shown to arrest lesion progression for over 10 years (Mertz-Fairhurst et al. 1998). 1999). increased understanding of the biological processes mediating tissue repair has allowed some investigators to mimic or supplement toothreparative responses. such as resin-modified glass ionomers. 2011 For personal use only. Toward this aim. In contrast. For larger penetrating lesions.which may be optimized. Mjör. It is primarily a bacterial disease. The goals of restorative therapy are to restore teeth to a state of health. Conversely.

diet. 1985). 2000a). have little or no caries-causing potential (Hillman et al. 1999). Currently. The secretion of reactionary dentin is the main postwas the most frequent reason for replacement of restorations... 2000).. attrition. The preservation of pulp vitality following restorative interwhich is approximately the annual proportion of restorative vention is dependent on the degree to which the pulpal cell treatments devoted to the treatment of caries (American populations can survive. and the importance of examining native approach to the eradication of caries may be to replace the effects of cavity preparation and capping materials on mutans streptococci with genetically altered strains.applying artificial enamel and ameloblasts to teeth is that this procedure provides a natural regenerative ability to respond to subsequent erosion. and the possibility of inducing tisThis demonstrates the different effects of restorative materisue cross-reactivity (Bleiweis et al. (D) GENE THERAPY TO VACCINATE AGAINST CARIES The eradication of dental caries or periodontal disease may be successful if gene transfer therapy can mediate humoral and cellular immune responses to the pathogenic bacteria involved in these disease processes (Slavkin. Age. International and American Associations for Dental Research 511 . This type of gene transfer therapy is called DNA vaccination. Maupome and Sheiham. and oral hygiene characteristics of patients injury has destroyed these primary cells (Fig. which pulp injury and regeneration. because of the difficulty of vaccination against intracellular organisms requiring cell-mediated immunity (Gurunathan et al.. as well as the ability of these cells to Dental Association. tion in response to a non-exposed cavity preparation. classified as being reactionary or reparative in origin.. 2000b). The process of tertiary dentin secretion can be ization and decay are under development (Robinson et al. 1996). bacterial leakage and secondary was formed. Reparative play a considerable role in restoration longevity. A review newly differentiated odontoblastoid cells (Smith et al. The most visible repair (III) Guidelines for Optimizing the Success of response to pulp injury is the deposition of a tertiary dentin Cavity Preparations matrix. 1b). If these techniques become introduced clinically.com by guest on March 18. operative odontoblast repair response to the presence of a followed by mechanical failures and various reasons such as cavity carefully cut into the dentin of a tooth (Fig. and reparative dentin is secreted by to investigate pulp reactions to existing treatments. 1990. 13(6):509-520 (2002) Crit Rev Oral Biol Med Downloaded from cro. is secreted by a second genercomplications such as hypersensitivity (Deligeorgi et al. tertiary dentin is focally secretNon-invasive approaches to the sealing of early caries lesions ed by odontoblasts in response to primary and secondary with penetrating adhesive resins to arrest tooth demineraldentin injury. Schematic representation of tooth injury and regeneration. abrasion.. of surveys found that secondary caries and/or discoloration 1995b). 1998. because DNA-containing antigens which can mediate an immune response are delivered in a plasmid to the target bacteria (Gurunathan et al. (A) IMPORTANCE OF PRESERVING PULP VITALITY The eradication of caries and bacterial disease could reduce the demand for restorative treatments by up to two-thirds.. Burke et al. the depending on the severity of the initiating response and the avoidance of operative intervention should greatly prevent conditions under which the newly deposited dentin matrix pulp injury. in contrast. A promising alterals on restoration longevity. in Arnst and Carey. (a) Pulp regenerasubsequent dental caries (Michalek et al. Unlike primary or secondary dentin that forms along the entire pulp-dentin border. Furthermore. this approach is years away to an exposed cavity preparation. 2001). Several surdentinogenesis is a much more complex process than reacveys have also showed how the placement of one type of tionary dentinogenesis. In the meantime. 1992). from clinical trials. which is functional prior to the appearance of their first teeth. (b) Pulp regeneration in response 2001)... 2011 For personal use only. 2000b). Minimizing pulp injury during cavity preparaal. as an effective way to induce immunity against the colonization of teeth by mutans streptococci and protection against Figure 1. or traumatic losses of tooth mineral.sagepub. ation of odontoblastoid cells when irreversible odontoblast 2001).. bacterial leakage and inflammation associated with healing Reparative dentin.. and is generally observed following restorative material in preference can make the critical differinjurious cavity preparation or a pulp exposure situation ence between success and failure within a few years (Mjör et (Mjör. No other uses without permission. reactionary dentin is secreted by precaries may also be avoided. Caries vaccine strategies may use the mucosal immune system in newborn infants. it is important existing odontoblasts. 1998). detect and respond to injury to initiate an appropriate repair response (Murray et al. 1a). In general.

Odontoblast survival and reactionary dentin secretion were the two responses most sensitive to cavity RDT (Murray et al. 1994). but also highlighted the importance of Erosion. particularly the cavity's remaining dentin thickness (RDT).. Following the in vitro culture of teeth (Murray et al. size. whereas patient variables and restorative factors had little effect (Murray et al. because this is less invasive than having to replace fillings completely. caries. International and American Associations for Dental Research ..2063 0.6794 0. the amount of pressure exerted on the handpiece (Hatton et al. The ability to understand and predict pulpal reactions to cavity preparation allows treatment decisions to be made which exploit the natural repair responses of the tooth. 1968) in addition to cavity RDT. pulp inflammation and cavity wall depth were influenced by cavity RDT. and the sequence of variables presented in Table 1 indicates aspects of treatment which are most deserving of attention in an attempt to minimize injury and optimize pulp dentin regeneration.0001 0. Although other variables were found to be less important (Table 1). 1996).. and diseases can severely injure teeth. 2002b). cavity conditioning treatment (Table 1). this finding is not to say that they lack effect in terms of pulp injury or healing. 2001). cavity conditioning. volume.0069 0. Deviations from the expected pulp responses to restorative treatment can be used to identify potential post-operative complications.. 1998). type. Investigation of pulp injury in in vivo human teeth confirmed the effects of some of these variables (Table 1). All aspects of restorative treatment require careful consideration. due to reductions in the protective properties of dentin. 1975). However. The relationship between these variables is shown in Fig. 2002a) and the choice of cavity restoration materials (Hilton. it has been frequently observed that greater injuries are sustained following cavity preparation and restoration with dental materials (Cox et al. Langeland and Langeland. The most influential variables in terms of causing pulp injury were the cavity's remaining dentin thickness (RDT). (C) PULP REACTIONS TO CAVITY’S REMAINING DENTIN THICKNESS Among the variables most important in the creation of pulp injury were the cavity remaining dentin thickness and type of restoration material (About et al. Consequently. restoration material temperature (Anil and Keyf.... No other uses without permission.2226 0. trauma. as well as the length of time the instrument is in contact with the dentin (Ohmoto et al.com by guest on March 18. 1998). and the use of cooling techniques (Lloyd et al. 2011 For personal use only. such as caries. (B) PULP INJURY AND HEALING RESPONSES TO CAVITY PREPARATION AND RESTORATION If pulpal viability and function are to be preserved.TABLE 1 Sequence of Cavity Preparation and Restoration Variablesa Correlated to Pulp Injury Cavity Preparation and Restorative Variable Correlations with Odontoblast Numbers as a Measure of Pulp Injury Cavity remaining dentin thickness Cavity wall depth Cavity wall area Pulpal inflammation related to RDT Type of restoration material Total cavity surface area Etching (cavity conditioning) Cavity volume Reactionary dentin area Sex of patient Cavity floor width Patient age Bacteria within restorations Cavity floor area Bacteria in cut dentinal tubules Time elapsed since operative procedures a Analysis of Variance (P value) 0.. however.0013 0... it is important to understand pulp reactions to a range of cavity preparation dimensions.3892 0. 2001). leading to hypersensitivity and allergic complications (Bergenholtz. 1992.5677 0. type of restorative material. 1975). and also from the chemical activity of dental materials (Lee et al.7557 selecting restorative materials which can prevent bacterial microleakage. because it maintains pulp cell function and viability. the cavity's remaining dentin thickness (RDT) (Stanley et al. 1992). 1994). some pulp effects of cavity preparation and restoration were examined. 2000c). cavity wall depth. these are commonly determined by the extent and progression of disease. (D) REPAIR OF FILLINGS RATHER THAN TOTAL REPLACEMENT An excellent method to conserve RDT is to repair faulty restorations. 1992) are important considerations. To a lesser degree.. and reduces the probability of postoperative pulp complications. Some investigations have found that the amount of intra-pulpal injury generated during cavity preparation and restoration is determined by the drill rotation speed (Hatton et al. 2002d).0001 0.. 1992...0044 0. and the presence of bacteria (Cox et al.. Deep cavities with small RDTs leave the pulp tissue less protected from preparation trauma. 1958.sagepub.0001 0. total cavity surface area. as well as by the cavity preparation form necessary to retain the filling. These findings confirm the observation that heat-energy is the most injurious event to pulp tissue (Zach. Practitioners need to have the option to re-attempt restorative treatment or develop a new treatment plan before post-operative complications can progress in severity and become irreversible. 1996). 1972). Kim and Trowbridge. area. 1990). to avoid stimulating pulp inflammation which can further injure the pulp tissue (About et al. inflammation related to RDT. While the dimensions of cavity preparations are under the control of the clinician. Pulp repair can be negatively influenced by the absence of coolant during cavity cutting. 1978). Stanley. 1994).. and cavity restoration must be assessed. and shape of the cutting instrument (Ottl and Lauer.0172 0. Reprinted with permission from the Journal of Dentistry. tion is clinically advantageous. the potentially injurious effects of cavity cutting.2211 0. Dentin protects pulp cells from potential sources of injury (Stanley et al. cavity preparation in the absence of coolant. 2002b). most dental schools are reluctant to teach students how to repair faulty restorations for 13(6):509-520 (2002) 512 Crit Rev Oral Biol Med Downloaded from cro.0001 0.0001 0. and the selection of restorative material if the pulp tissue is exposed (Murray et al. Other potential sources of pulp injury during cavity restoration include: conditioning of the dentin cavity walls with acid etchants (Murray et al. and the bur speed (Swerdlow and Stanley. 2. The effects of RDT on odontoblast survival and reactionary dentin repair activity can be attributed to an increasing degree of cellular injury.

(E) RESTORATIVE MATERIALS FOR NON-EXPOSED CAVITY PREPARATIONS Patient confidence is promoted by the placement of long-lasting restorations not subject to recurrent caries.. or symptoms requiring endodontic treatment. Inflammation has been shown to produce a down-regulation of normal sodium channels in nerves (Waxman et al. 1986.sagepub. such as those that are newly erupted. most restorative materials appear to mediate low levels of pulp inflammation in teeth with highly permeable dentin. except in the presence of bacterial leakage (Cox et al. (F) PULP INFLAMMATION AND BACTERIAL LEAKAGE ASSOCIATED WITH RESTORATIVE MATERIALS The immune system triggers inflammatory reactions to limit tissue damage from invading or foreign molecules (Jontell et al. The selection of restorative materials has an important influence on bacterial leakage. 2001). of these restorations (Table 2). this technology allows sufficient image quality for the removal of carious tooth structure. allergic sensitization. Pashley. 1996).. Zinc oxide eugenol and resin-modified glass ionomer can prevent bacterial growth in 100% of cavity restorations for up to one year following treatment (Table 2). 2000). personal communication). 1998). 1999) and surgical skill remain important for influencing treatment success. Recognition over the last few years that the largest proportion of restoration failures arises from secondary (recurrent) caries or complications (Deligeorgi et al. most likely due to the need for restorations to be finished with a very high technical quality (Murray et al. Reprinted with permission from the American Journal of Dentistry. Operator handling (Ciucchi et al. Finger and Balkenhol. personal communication).. mechanical. Severe forms of inflammatory activity can develop into total pulpal necrosis and periapical lesion development with local bone destruction (Bergenholtz. However. Pulp injury and repair activity increas as the remaining dentin thickness decreases (Murray et al. Murray et al.. Summary of human pulp responses to the remaining dentin thicknesses of cavity preparations.. several surveys have showed how the selection and placement of one type of restorative material in preference over another can make the critical difference between the failure and the success of treatment within a few years (Maryniuk and Kaplan. it is possible to illuminate and visualize these areas under magnification on a video monitor. 1999). No other uses without permission. International and American Associations for Dental Research 513 . sealing of the cariesaffected dentin. 1997.. 2011 For personal use only. 2000. Another part of the problem is the clinician's inability to visualize gingival or subgingival marginal areas. 2002c). 2000. the inflamed pulp is associated with hypersensitivity. before they begin using them clinically (D. Bergenholtz.. This often leads to the removal and replacement of functional restorations simply to repair a marginal defect affecting perhaps only 10% of the restoration. Figure 2. so that thermal. 2002c). The placement of enamel-bonded resin composite and adhesive-bonded resin composite does not seem to result in a perfect seal with cavity walls. extensive decay will be overlooked. 1966. Burke et al. Okiji et al. 2001) has led to technological advancements in dental materials.fear that they would be regarded as second-class restorations or that severe.. 2000).H. Part of the problem involves the philosophy of seeking ideal treatment. Cavity preparation trauma as well as the chemical activity of restorative materials can stimulate the release of inflammatory mediators from sensory nerve fibers (Langeland et al. However. or osmotic stimuli encountered in normal function can cause intense pain (Ngassapa. Tarim et al. respectively. Pashley. These inflammatory reactions can injure the pulpal cell populations and lead to pulp complications in response to cavity restorations that may initially appear to be successful (About et al.. 1982).. In less severe cases. and repair of the faulty filling according to the principles of minimally invasive dentistry (D. It is a pity that many student dentists do not have laboratory exercises where they can perfect their bonding technique by measuring bond strengths to teeth bonded in vitro. 1999).. because bacteria were detected in 24 and 11%. 1982. Together with staining with caries-detector solutions.com by guest on March 18. These observations can be attributed to the antibacterial activity of these agents and the direct sealing of cavity walls (Bergenholtz et al. These observations explain why immunological inflammatory activity is associated with the high rates of primarily vital teeth exhibiting pulpal complications following cavity 13(6):509-520 (2002) restoration (Zöllner and Gaengler. pulp inflammation.H. 1997). 1998).. The favorable sealing characteristics of resin-modified glass ionomers explain why these materials are recommended for Crit Rev Oral Biol Med Downloaded from cro. 1987. However. using the same fiber-optic devices that are used in periodontics and endodontics. 2001).. in an attempt to reduce their leakage characteristics and improve their longevity (Kugel and Ferrari..

mechanical or traumatic injury compromises the pulp-healing response (Mjör.. Fitzgerald et al. 1998. cultures of pulp fibroblasts did not appear to differentiate into cells with odontoblast-like phenotypes or secretory characteristics (Hanks et al. The most important factor in this decision-making process is the likelihood of success. while the success of non-exposed cavity preparation/restorations is generally much higher and varies with different types of materials and conditions (Maupome and Sheiham. 2000. The source of these cells has proved to be a source of much speculation. 2000).. but it is reported to be 37% after 5 years and 13% after 10 years (Barthel et al.TABLE 2 Pulpal Inflammatory Activity and the Presence of Bacteria at the Tooth-Restorationa Interface Pulpal Inflammation (Percentage of Teeth) Restorative Material Composite resin bonded to dentin Composite resin bonded to enamel Resin-modified glass ionomer Zinc oxide eugenol Calcium hydroxide a Bacterial Leakage (Percentage of Teeth) Severe 9 6 0 0 0 No 89 76 100 100 Yes 11 24 0 0 - Absent/Slight 32 38 51 91 83 Moderate 59 56 49 9 17 These restorations were placed in the caries-free teeth of young adult patients. 2000). 2000). 1978. Consequently. 2000. Second. These cells appear to migrate to the site of pulp exposure and secrete reparative 13(6):509-520 (2002) 514 Crit Rev Oral Biol Med Downloaded from cro. (A) PULP-CAPPING THERAPY Class V cavities in caries-prone patients (Bergenholtz et al. International and American Associations for Dental Research . The detection of bacteria beneath composite resin restorations demonstrates the continued need for improvement in the adherence and marginal sealing ability of these materials.. lack of pre-existing symptoms. Hafez et al. Fourth. while identifying and removing diseased or infected tissue (Hafez et al. operative debris including dentin fragments.b). Third. 1994. these primary cells must be replaced by a new generation of odontoblastoid cells (Tziafas. 2011 For personal use only. or the opposite effect: The excessive formation of tertiary dentin can be associated with a closure of the pulp chamber and root canals (Stanley. 1990).. sometimes called "chipitis" (Stanley. 1998. 1998). The failure to form tertiary dentin may leave pulp tissues vulnerable to subsequent injury. there is an 86% success rate for equivalent teeth over 10 years for teeth that did not have a pulp exposure prior to restoration (Mertz-Fairhurst et al. The success of pulp capping depends on many factors (Mjör. 2000). where reparative dentin is secreted (Fitzgerald et al.. MacDougall et al. Nevertheless. 1990). open tooth apex.. Tissue engineering may be able to revitalize pulp tissues by adding new stem cells or by transplanting new vital tissue. Severe inflammation was avoided by the use of materials such as resin-modified glass ionomer and zinc oxide eugenol that prevented bacterial growth (Murray et al. all primary odontoblasts are irreversibly injured at the exposure site (Murray et al. terminally differentiated cells cannot proliferate to replace subjacent irreversibly injured odontoblasts. Autoradiographic studies have indicated that new odontoblastoids proliferate from within other pulp cell populations by a process of differentiation and migrate toward the site of pulp exposure.. good patient health.. Factors which contribute to the likelihood of pulp-capping success include a young patient age. (IV) Guidelines for Optimizing the Success of Pulp-exposed Cavity Preparations The difference between the longevity and frequency of complications associated with exposed and non-exposed pulp restorations means that it is worthwhile to make every effort to avoid creating pulp exposure.. 1989). Inc . Reprinted by permission of ADA Publishing. Górecka et al. it is necessary to control hemorrhage that contaminates the dentin surface and prevent blood clot formation. The prevention of bacterial microleakage will limit the severity of pulp inflammation and help maintain pulp tissue vitality... the clinician must decide whether to place a pulp-capping material or to undertake pulpotomy. 2000).. It would seem that restorative materials that form the most perfect sealing with tooth structure are most able to prevent bacterial microleakage. 1995)... Until such approaches are available. the presence of dentin restricts the diffusion of potentially injurious agents in deep dentin. These post-mitotic. during surgery. good pulp response to stimuli. and minor pulpal hemorrhage (Christensen. small size of exposure. Hørsted et al. however. First. and particles of capping materials may infiltrate the pulp. 2001b).. © 2001 American Dental Association.. after the pulp is exposed. es the pulp tissue to be more sensitive to the possible cytotoxic and irritational action of the capping agent (Murray et al. 1999). 1998). The loss of dentin beneath the restorative material caus- (B) ODONTOBLAST REPLACEMENT BY ODONTOBLASTOID CELLS Following pulp exposure.com by guest on March 18. recent histological investigations have observed the presence of pericyte and myofibroblast transitional cells in pulp tissue (Carlile et al. by the use of sandwich placement techniques to reduce composite resin shrinkage during polymerization (Gallo et al. Possible progenitor cell populations for the new odontoblastoid cells were assumed to be the subjacent cells of the sub-odontoblast layer or pulp fibroblasts (Fitzgerald. 1981). Most dentists will immediately opt for a pulpotomy (Ranly and Garcia-Godoy. However.sagepub.. 1998). to make future endodontic treatment difficult or impossible. 1979. only 50% of the dentin surface is composed of tubules. 2001). a Division of ADA Business Enterprises.. 2000e). it is important to use direct pulp-capping materials and placement techniques which will benefit pulp healing and preserve pulp vitality. Ultimately. No other uses without permission. while the other half is made up of solid buffer. 2001). However. The greater prevalence of bacteria in cavities following use of enamel-bonded resin composite suggests that inadequate or incomplete bonding to dentin may result in increased leakage of bacteria at the tooth/restoration interface. causing injury and inflammatory reactions (Walton and Langeland. Alliot-Licht et al. 2001). 1998. Pulp exposures are more problematic to restore than nonexposed pulp cavity preparations for several reasons. 2002a. Burke et al. 1982).

Calcium hydroxide may be considered to be a comparatively primitive material by current standards. 1994.sagepub. 2002). degree of mechanical injury.. it must be recognized that the placement protocols for adhesive systems are not fully optimized. the selection of materials with the ability to seal the exposed pulp and prevent bacterial leakage is perceived as the most important factor in avoiding and minimizing pulp inflammation. step 3. which allows for passage between the exposure site and pulp tissue (Cox et al. and improvements are needed to increase the ease and speed of placement. for more complete bridging of pulp exposures.com by guest on March 18. over the same time. The first generations of calcium-hydroxide-containing materials had improved physical properties but were still not insoluble. by injury or the age of the patient. 2002e).. 1994). Consequently. Currently.. and osteoblasts (Schor et al. Its use is largely based on histological evidence. The high pH of calcium hydroxide provides bactericidal activity and encourages tissue repair by promoting tertiary dentin secretion (Yoshiba et al. these cells offer exciting opportunities for regenerating decayed dentin for which there are few conservative treatment possibilities because of the limitations of current treatment options. The similar phenotype between normal fibroblasts and odontoblastoid progenitor cells probably explains why the identification and activity of these cells have proved difficult to isolate. 1997). Foreman and Barnes. polymerization-shrinkage during the placement of these materials can create marginal gaps to permit bacterial leakage to occur (Pashley. be developed include: using bioactive molecules to mediate pulp repair (Tziafas et al.. Isolation of these cells in culture has produced human dentin secretion (About et al. 1990). as well as active cariesprevention activity (Christensen. 1994). including desensitizer. 1996).. 2002e).and hard-tissue phenotypes. The presence of operative debris appears to interfere with the continuity of dentin bridging. If teeth require extraction. referred to as dentin bridge formation (Cox et al... 1996). such as smooth muscle (Meyrick et al. improving sealing and bond strengths (Costa et al. Recently. To act as an effective barrier against bacterial leakage and migration of particles from capping materials. which may develop into necrosis (Walton and Langeland.. 1997). 2000.. 2000).. No other uses without permission. they initially appear to be pluripotent mesenchymal cells with the potential to express both soft. Moreover.dentin (Murray et al. 1990). 1987). 1994). the reparative dentin should not contain any tunnel defects (Cox et al. 2002e). 47. 1996). However. Consequently... This same approach should also be applied to stimulate healing of pulp tissues if pulp-reparative activity is compromised—for example. This is because globules of resin can migrate into pulp tissue and stimulate inflammation (Kitasako et al. step 5). 1981). thus causing inflammation. and preventing or arresting root resorption (Mjör and Ferrari. 1978). International and American Associations for Dental Research 515 . 2001). Even Crit Rev Oral Biol Med Downloaded from cro. 1b.. fibroblasts (Ivarsson et al.. such as: inducing healing of periradicular lesions.. 2001). and they eventually permitted bacterial leakage to occur (Cox and Suzuki.. chondroblasts (Diaz-Flores et al. In addition. and 25% of them are dissatisfied (Lechner and Roessler. promoting apical closure in incompletely developed teeth. The secretion of dentin bridges can be influenced by pulp-capping materials. The adhesive systems used to place composite resin materials appear to have more technological development potential. These findings agree with reports suggesting that new composite resin products are superior to their predecessors in having improved sealing properties.) While these cells appear to lack some characteristics of true stem cells. Future areas in which these adhesive systems could 13(6):509-520 (2002) (V) Impact of Tissue Engineering on Restorative Dentistry (A) THE PROBLEM OF NON-RESTORABLE TEETH The treatment of caries and periodontal diseases has improved greatly over the last 50 years and has led to reductions in the numbers of teeth extracted (Greenberg. 2000). 1b. 1981).0 %) (Murray et al. 1996). The leakage of bacteria was highly correlated with pulp inflammation in the teeth of young adults (Murray et al. 2001). A tunnel defect is a discontinuity in the structure of reparative dentin.. patients have the option of having artificial tooth implants fitted or wearing dentures. slow bur speeds should be used together with the cleansing of operative debris from the site of exposure. Inflammation and bacterial leakage also negatively influence dentin bridge formation (Cox et al. Growth factor therapy is already used to promote new bone formation to correct periodontal defects (Heijl et al. These specialized fibroblast-phenotype pulp cells have the ability to migrate in response to cytokine signaling molecules (Ellis et al.. 2002e). (A schematic representation of these cells is shown in Fig. the introduction of new composite resin materials has provided various options for the restoration of indirect cavity preparations (Cox and Suzuki... Consequently. 1994). 2000). 1999). 1987.7% vs. A comparison between pulp capping with resin composite and that with calcium hydroxide showed that composite resin was associated with a lower frequency of bacterial leakage (19. it was observed that most tunnel defects are associated with operative debris or particles of capping materials (Murray et al. 2002e). and the creation of dentin debris during operative procedures (Murray et al. adding antibacterial activity (Imazato et al. and to avoid problems.. 1996). Knowing the benefits and problems associated with these restorative materials is helpful in assessment of the risks and types of post-operative complications. calcium hydroxide suffers from unstable physical properties that allow material particles to migrate into pulp tissue. A practitioner's attention to minimizing operative debris and carefully placing pulp-capping materials is postulated to be most beneficial for dentin bridge formation (Cox and Suzuki. 2011 For personal use only. (E) PULP INFLAMMATION FOLLOWING DIRECT PULP CAPPING (C) DENTIN BRIDGE FORMATION Dentin bridges are a type of tertiary dentin secreted by odontoblastoid cells at the site of pulp exposure (Fig. 45 million Americans wear dentures. (D) PULP-CAPPING MATERIALS The selection of direct pulp-capping materials and treatments has changed little in the past 30 years while. Calcium hydroxide is the most commonly used pulp-capping agent (Yoshiba et al... 1992). (F) TUNNEL DEFECTS The pulp tissue can be protected following exposure by the deposition of tertiary dentin. Both composite resin and calcium hydroxide pulp capping appeared to have similar effects on pulp inflammation in the presence and absence of bacteria. Alliot-Licht et al.

1997). then some obvious applications of the tissue engineering discussed previously in this review become apparent. and where to start. radiographs. No other uses without permission. technical problems. or accidentally evulsed tooth. Large Loss of Vital Tissue Partially decayed or fractured tooth Complete Loss of Vital Tissue Decayed tooth. Stimulate pulp-dentin healing with growth factors. 2002a. Pulp capping.. pulp regeneration will be used as the basis for tissue engineering to radically alter restorative dentistry and the prognosis of restored teeth. when. if we examine restorative dentistry by the degree of tooth injury requiring restoration. From the biological perspective. there will always be some teeth that are too severely damaged to be restorable.sagepub. Restorative materials may contain a "cocktail" of growth factors. Although restorative dentistry is too highly dependent on clinical opinion to be an exact scientific discipline (Mjör. likely tissue-engineering therapies are shown in Table 3. each restorative variable has some effect on pulp vitality. 2000c. Use progenitor cells and growth factors in 3-dimensional tissue culture to harvest artificial teeth for implantation. cavitycutting methods. 2000). Deviations from normal pulp regeneration may be used to diagnose the onset of complications. and these will still require extraction and replacement. Examples of tooth injury with common restorative treatments vs. 2001a). 2000. and there is no way of knowing how successful these therapies will eventually prove to be. 13(6):509-520 (2002) 516 Crit Rev Oral Biol Med Downloaded from cro. Eventually. 2002d) and human dentin to be synthesized and secreted in vitro (About et al. Recent developments in tissue-culturing technology and improvements in controlling oral cell activity have facilitated the growth of teeth in organ culture (Murray et al.TABLE 3 Summary of Tooth Injury and Possible Applications of Tissue-engineering Approaches to Aid Healing Degree of Tooth Injury Example of dental problem Some Loss of Vital Tissue Arrested or slowly progressing caries lesion extending to pulp tissue Stepwise excavation of caries lesion. studies are under way with proteins to improve gingival adhesion to implants (Tamura et al. such as bacterial leakage and pulp inflammation. and patient opinions to be used for predicting the outcomes of different caries-treatment strategies. endodontic treatment. Minimizing pulp injury during cavity preparation and placing materials which prevent bacterial microleakage will preserve pulp vitality. or pulp capping Regenerate lost tissues and dentin repair with growth factors. In the meantime. and vice versa for when to stop.com by guest on March 18. Conclusion Tissue-engineering therapies offer exciting treatment possibilities.. Alter oral bacterial DNA to arrest and prevent subsequentenamel and dentin caries demineralization. (VI) Summary Restorative dentistry is an intricate form of microsurgery. but health hazards. International and American Associations for Dental Research . pluripotent cells may be implanted to regenerate tooth structure. The following guidelines are intended to avoid the need for restorative treatment. To avoid the need for operative dentistry. DNA vaccines may be used to arrest or prevent the development of caries lesions. in any review of this type. This explains a general reluctance of authors to be specific and speculate on how tissue engineering will transform individual aspects of restorative dentistry (Ranly and Garcia-Godoy. injury. it is often difficult for clinicians to know how. restorative dentistry will rely on the optimization of conventional therapies. The next stage in this process will be to grow and harvest artificially grown teeth as a substitute for implants and prosthodontic devices once teeth have been extracted. the issue of using therapies in situations where they are likely to prove most beneficial should be addressed. and regeneration. avoid the creation of pulp exposures. Yet there are biological indicators as well as records of longevity for restorations. But injury to original tooth-supporting structures from disease and tooth extraction will likely compromise the success of tooth transplantation. Mjör. Furthermore. stimuli testing. Common current restorative therapy Seal fissure or excavate caries and apply restorative materials. 2011 For personal use only. delivered in a slow-release vehicle to regenerate replacement dentin from intra-coronal pulp matrix. (B) POTENTIAL APPLICATIONS OF TISSUE ENGINEERING TO REPLACE EXISTING THERAPIES There appears to be no certainty regarding the introduction of any particular aspect of tissue-engineering therapy into restorative dentistry. Likely objective of tissue engineering in restorative therapy with the implementation of tissue-engineering procedures in restorative dentistry. However. and restorative materials. In cases of partially decayed or fractured teeth. However. and optimize restorative outcomes. It is hoped that this research will also benefit tooth implantation. Minimal Early non-arrested caries lesion Severe Arrested deep-penetrating caries lesion Excavate caries and apply restorative materials.b). Remove injured tissue and place implant or prosthetic teeth. non-restorable or lost and missing teeth might be replaced by artificial implants of tooth tissues grown synthetically in an in vitro culture. When removing caries. and high costs will delay their routine introduction for years to come. or tooth extraction Implant progenitor cells to regenerate lost tissue and tooth mineralized structure..

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